The Study On Structure Modification Of Indirubin And Antitumor Bioactivity Evaluation On Its Derivatives

Indirubin is one of the major physically active compounds of traditional Chinese medicine Qingdai,it can prohibit the synthesis of the DNA of cancer cell due to its unique chemical structure.Organocatalysis is a safe,nontoxic,stable and reliable way which usually enables high yield.Recently,asymmetric synthesis promoted by organocatalysis,especially in the application of the construction of chiral durg-like compounds,attracts organic chemists and pharmaceutical workers enormously.Inverse-Electron-Demand-Oxa-Diels-Alder reaction is a powerful strategy which furnishes dihydropyran compounds.In this work,we constructed a series of 2-arylidene-indolin-3-one,the derivatives of indirubin,based on the C2 position of indole,according to the chemical structure of indirubin.We promoted the Inverse-Electron-Demand Oxa-Diels-Alder reaction between Z-2-benzylidene-1-phenylsulfonyl-indolin-3-one and enolizable aldehyde under the catalysis of chiral diphenyl prolinol trimethylsilane ether through the enamine intermediate.We had screened all the factors that affected the reaction and synthesized the chiral indole[3,2-b]tetrahydropyrans with both high enantioselectivities and diastereoselectivities and in good yields under the optimized reaction conditions.Then we explore the scope of substrates,heteroaryl and aryl bearing electron-donating or electron-withdrawing groups were well tolerated under the best reaction conditions.Furthermore,we study the the effects of different configurations of the 2-benzylidene-1-phenylsulfonyl-indolin-3-one and various N-protecting groups on this reaction.We build various indole[3,2-b]tetrahydropyrans with different chemical structures in the end.After finishing the chemical work,we selected five kinds of the most hazardous malignant cells(A549,MCF-7,Hep G2,HCT116,U87)so as to test the activities of representative compounds 8a,8q,8r,8s,8t,8x,8w,9,10,11 through MTT method.However,the best inhibition ratio turned out to be 81.55% under the concentration of 50?M,which is not satisfactory from our perspectives.We envisage that the deprotection of the N atom will increase the the compounds' activities and this hypothesis is under experiment in our lab.